LoQus23 Therapeutics nominates LQT-23 as first-in-class, oral drug candidate for Huntington's Disease

• LQT-23 is a potent, highly differentiated, first-in-class allosteric small molecule inhibitor of MSH3/MutSβ
• Unique mechanism of action with potential to slow or stop the progression of HD

CAMBRIDGE, England, Jan. 6, 2026 /PRNewswire/ -- LoQus23 Therapeutics Ltd ("LoQus23"), a biotechnology company investigating small molecule drugs that could stop the pathogenic triplet expansion that is the cause and driver of Huntington's Disease (HD), myotonic dystrophy type 1, and other triplet repeat expansion diseases, today announces that it has nominated, and is progressing, LQT-23, a drug candidate which has groundbreaking potential to slow or stop the progression of HD.

DNA mismatch repair has been shown as a key driver of HD and other triplet repeat diseases. Convergent evidence from human genetics, post-mortem studies, and mechanistic research identifies MSH3/MutSβ as the most promising target of the DNA mismatch repair pathway. However, the protein is a highly challenging target for small molecule therapeutic intervention.

By leveraging its deep expertise of the pathway and the disease, LoQus23 has established a platform of assays and multiple series of small molecule MutSβ inhibitors. LQT-23 represents a groundbreaking advancement in MutSβ modulation for the treatment of HD, employing a novel mechanism of action to inhibit this complex target. LQT-23 is the most advanced and potent allosteric small molecule inhibitor of MutSβ to date.

Dr David Reynolds, Chief Executive Officer of LoQus23 Therapeutics, commented: "The nomination of LQT-23 as our development candidate is a significant moment for LoQus23 and reaffirms our strategy of advancing our pipeline of MSH3/MutSβ inhibitors to transform the lives of patients. I want to salute the dedication of our team which has worked tirelessly over many years to identify this candidate for such a difficult target, and we look forward to advancing it to IND/CTA filing later this year."

Dr Cyrus Mozayeni, Chair of the Board of Directors of LoQus23, added: "MSH3/MutSβ is the most promising and best validated target for HD, but has been difficult to drug. The team has made exceptional progress since the financing in 2024, and the nomination of LQT-23 as our lead development candidate underscores our deep domain expertise, while positioning LoQus23 at the forefront of emerging therapies for the treatment of HD."

Preclinical studies of LQT-23 have demonstrated potent and selective modulation of MSH3/MutSβ which leads to robust blockade of somatic expansion in HD cellular systems and animal models. Pre-clinical development will continue through 2026.

Huntington's disease is an autosomal dominant neurodegenerative disorder for which there is currently no approved disease modifying treatment and which has 30,000 patients in the US alone. By targeting somatic expansion, LoQus23 is hoping to slow or even halt the onset and progression of Huntington's disease. In 2024, LoQus23 announced the successful close of its £35 million Series A financing round led by Forbion, alongside existing investors SV Health Investors' Dementia Discovery Fund and Novartis Venture Fund.

Notes to Editors

About LoQus23 Therapeutics Ltd
LoQus23 is a biotech company based in Cambridge, UK, developing small molecule somatic expansion inhibitors for the treatment of Huntington's Disease and other triplet repeat expansion diseases. Huntington's disease is an autosomal dominant neurodegenerative disorder for which there is currently no approved disease modifying treatment and which currently has 30,000 patients in the US alone.

LoQus23's approach has the potential to stop DNA instability and therefore slow neurodegeneration in these diseases. LoQus23 is focused on using a structure-based approach to design small molecule drugs, which can offer more convenient administration than other approaches. Oral small molecule drugs have a strong track record in treating complex brain diseases and provide greater convenience for patients compared with other advanced treatment modalities. LoQus23's lead programme, a potent allosteric small molecule MSH3 inhibitor, part of the MutSβ complex which is now entering preclinical development.

LoQus23 has a highly experienced leadership team, built on world-class science. It was originally established in 2019 by Dr David Reynolds, Dr Caroline Benn, and Dr Ruth McKernan CBE, FMedSci, Entrepreneurs in Residence at SV Health Investors' Dementia Discovery Fund, which also acted as the initial seed investor. In October 2024, the Company closed a successful £35 million Series A financing round led by Forbion, alongside existing investors SV Health Investors' Dementia Discovery Fund and Novartis Venture Fund.

For more information, please visit: www.loqus23.com